The immune system is comprised of innate and acquired immunity, both of which work cooperatively to protect the host from microbial infections. It has been shown that innate immunity can recognize conserved pathogen-associated molecular patterns through toll-like receptors (TLRs) expressed on the cell surface of immune cells. Recognition of invading pathogens then triggers cytokine production (including interferon alpha (IFNα)) and upregulation of co-stimulatory molecules on phagocytes, leading to modulation of is T cell function. Thus, innate immunity is closely linked to acquired immunity and can influence the development and regulation of an acquired response.
TLRs are a family of type I transmembrane receptors characterized by an NH2-terminal extracellular leucine-rich repeat domain (LRR) and a COOH-terminal intracellular tail containing a conserved region called the Toll/IL-1 receptor (TIR) homology domain. The extracellular domain contains a varying number of LRR, which are thought to be involved in ligand binding. Eleven TLRs have been described to date in humans and mice. They differ from each other in ligand specificities, expression patterns, and in the target genes they can induce.
Ligands which act via TLRs (also known as immune response modifiers (IRMS)) have been developed, for example, the imidazoquinoline derivatives described in U.S. Pat. No. 4,689,338 which include the product Imiquimod for treating genital warts, and the adenine derivatives described in WO 98/01448 and WO 99/28321.
WO2009/067081 describes a class of pyrimidine derivatives having immuno-modulating properties that act via TLR7 which are useful in the treatment of viral or allergic diseases and cancers.
4-(Dimethylamino)butyl 2-(4-((2-amino-4-methyl-6-(pentylamino)pyrimidin-5-yl)methyl)phenyl)acetate and certain salts thereof are described in Example 57 of International Patent Application No. PCT/SE2008/051334 filed on 21 Nov. 2008, published as WO2009/067081.